Nasal Administration of Dolutegravir Loaded Nanoparticles Based Mucoadhesive in situ Gel: Design and in vivo Assessment

Abstract:

Background: To assess the potential for targeting the brain through intranasal delivery, this study focuses on optimizing and developing a mucoadhesive in situ gel formulation containing Dolutegravir nanoparticles. Materials and Methods: Employing a central composite design, the study optimized the concentration of variables of Hydroxypropyl methylcellulose (HPMC, X₁) and Poloxamer 407 (X₂) on the gelation temperature (Y₁) and drug release (Y₂). The optimized drug loaded nanoformulations were assessed for various pharmaceutical features, in vitro release and evaluated in vivo. Results: Both variables significantly impacted the responses (p<0.05). The selected formulation displayed beneficial rheological characteristics and prolonged drug release. In vivo pharmacokinetic analysis in rats post-intranasal administration of the optimized in situ gel demonstrated markedly higher (p<0.0001) C_max (2-fold) and AUC0-t (3-fold) values in the targeted brain tissue as compared to intravenous administration. Reduced Dolutegravir exposure in the central compartment validates limited absorption with nasal therapy. Conclusion: The study affirms the potential of the in situ mucoadhesive nasal gel in delivering Dolutegravir to the brain. Thus, the optimized nasal gel emerges as a promising therapeutic alternative for Neuro AIDS by efficiently delivering Dolutegravir to the brain.

Keywords: Dolutegravir, in situ gel, Nasal route, Brain, in vivo.